What is N-Acetylsulfanilyl chloride used for?

N-Acetylsulfanilyl chloride is an important intermediate in the dye and pharmaceutical manufacturing industries and is also widely used in coatings, plastics, pesticides, and other fields.

The industrial production of N-Acetylsulfanilyl chloride mainly includes two processes: direct chlorosulfonation with chlorosulfonic acid and the chlorination of p-acetylaminobenzenesulfonic acid. The direct chlorosulfonation method involves sulfonation and chlorination reactions with chlorosulfonic acid and acetanilide to produce N-Acetylsulfanilyl chloride. The chlorination of p-acetylaminobenzenesulfonic acid involves using chlorosulfonic acid or sulfur trioxide for sulfonation, followed by chlorination with reagents like thionyl chloride, phosphorus pentachloride, oxalyl chloride, or phosphorus oxychloride to obtain N-Acetylsulfanilyl chloride.

What is N-Acetylsulfanilyl chloride used for?

Role in Pharmaceutical Manufacturing

N-Acetylsulfanilyl chloride is an intermediate in various sulfa drugs, such as sulfathiazole, sulfisoxazole, sulfamethoxazole, sulfapyridine, and sulfadimethoxine. N-Acetylsulfanilyl chloride is a key intermediate for several sulfa drugs, as listed below:

Dye Intermediate

N-Acetylsulfanilyl chloride is a crucial intermediate in the dye industry. Joonseok Koh and colleagues synthesized a series of alkali-clearable azo disperse dyes containing fluorosulfonyl groups. Various 4-fluorosulfonyl anilines used as diazo components were prepared by coupling N-Acetylsulfanilyl chloride with the corresponding coupling components, resulting in 4-(N, N-diethylamino)-4'-fluorosulfonyl azobenzene dyes.

Antigen Synthesis

L-Hydroxyproline is a special amino acid found in hydrolyzed animal proteins. L-Hydroxyproline is derivatized with N-Acetylsulfanilyl chloride and 5-chlorovaleric acid to synthesize haptens HP1 and HP2. Subsequently, two immunogens are prepared from these haptens to produce antibodies. The results show that only HP1 can stimulate the animal immune system and produce specific antibodies against L-hydroxyproline (as the formation of HP1). The monoclonal antibodies obtained with HP1 and heterologous coated hapten HP2 were incorporated into a competitive indirect enzyme-linked immunosorbent assay (ELISA) to determine antibody specificity and sensitivity. The IC (50) and detection limit for HP1 were 0.16 μg/mL and 0.05 μg/mL, respectively. The antibody showed low cross-reactivity with the parent L-hydroxyproline and negligible cross-reactivity with D-hydroxyproline and other amino acids. Therefore, this monoclonal antibody is suitable for developing immunoassays to monitor hydrolyzed animal protein in solid leather waste with L-hydroxyproline as the target analyte in food.

Drug Screening

N-Acetylsulfanilyl chloride has been studied for screening patients undergoing colonoscopy screening or monitoring.

Pharmacokinetics

Due to the widespread use of sulfonamide antibiotics (SAs), it has become a ubiquitous environmental pollutant, raising public concern. However, the comprehensive understanding of these pollutants in complex environmental systems has been hindered due to the unavailability and high cost of isotopically labeled SAs. N-Acetylsulfanilyl chloride can be used to synthesize internal standards for determining drugs and their metabolites in biological samples.

Xuan Wu and others synthesized [14C]- and [13C]-labeled sulfonamides (SMX, SMM, and SDZ) starting with commercially available [14C]- and [13C]-labeled aniline. The synthesis involved four steps (condensation of labeled N-Acetylsulfanilyl chloride and aminoheterocycles), yielding good (5.0–22.5% and 28.1–54.1% for [14C]- and [13C]-labeled SAs) and high-purity products (>98.0%). Milligram-scale synthesis of [14C]-labeled SAs can produce labeled SAs with high specific radioactivity. This method can be used to produce various [14C]- or [13C]-labeled SAs to study their environmental behavior, including the fate, transformation, and bioaccumulation of these antibiotics in soil and water systems.

Organic Synthesis

N-Acetylsulfanilyl chloride is used as an organic building block in synthesizing various organic compounds. Nucleoside derivatives have played an essential role in treating multiple diseases. Considering the importance of nucleoside analogs, Asraful Alam and colleagues synthesized a series of nucleoside molecules, namely uridine derivatives. The uridine molecules were acylated directly with N-Acetylsulfanilyl chloride to obtain the corresponding 5'-ON-acylsulfonamide uridines with the ribose portion.

Stable Isotope Synthesis

Synthesizing stable isotopes (e.g., 13C, 15N) plays a significant role in mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy studies, primarily for quantifying and identifying pollutants and their metabolites in complex matrices. In these studies, N-Acetylsulfanilyl chloride plays a crucial role.

Safety

N-Acetylsulfanilyl chloride is classified as a skin-corrosive chemical that can cause severe skin burns and eye damage. It may also irritate the respiratory tract.

N-Acetylsulfanilyl Chloride SDS Important Information

First Aid Measures

• General advice: Consult a doctor. Show this safety data sheet to the attending physician.
• If inhaled: Is inhaled, move the person to fresh air. If not breathing, give artificial respiration. Consult a doctor.
• If skin contact: Wash off with soap and plenty of water. Consult a doctor.
• If eye contact: Rinse thoroughly with plenty of water for at least 15 minutes and consult a doctor.
• If swallowed: Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a doctor.

Accidental Release Measures

• Personal precautions, protective equipment, and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid inhalation of vapors, mist, or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
• Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let the product enter the drains. Discharge into the environment must be avoided.
• Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Handling and Storage

• Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.
• Conditions for safe storage, including any incompatibilities: Store in a cool place. Keep the container tightly closed in a dry and well-ventilated place.

Personal Protection

Wear protective gloves/protective clothing/eye protection/face protection.

References:

[1]Wang L L, Liu J X, Liu J, et al. Synthesis of hapten and production of a monoclonal antibody against a derivative of L-hydroxyproline, a special amino acid in hydrolyzed animal protein[J]. Journal of Environmental Science and Health, Part B, 2013, 48(1): 9-15.

[2]https://go.drugbank.com/drugs/DB12337

[3]Wu X, Yao Y, Wang L, et al. Synthesis of typical sulfonamide antibiotics with [14C]-and [13C]-labeling on the phenyl ring for use in environmental studies[J]. Environmental Sciences Europe, 2022, 34(1): 23.

[4]Alam A, Hosen M A, Islam M, et al. Synthesis, Antibacterial and cytotoxicity assessment of modified uridine molecules[J]. Curr. Adv. Chem. Biochem, 2021, 6: 114-129.

[5]Koh J, Greaves A J, Kim J P. Synthesis and spectral properties of alkali-clearable azo disperse dyes containing a fluorosulfonyl group[J]. Dyes and pigments, 2003, 56(1): 69-81.

[6]Shijiazhuang Hehe Chemical Fertilizer Co., Ltd., Beijing University of Chemical Technology. A continuous preparation method, device and system for 4-acetamidobenzenesulfonyl chloride: CN202211309117.9[P]. 2023-10-27.

[7]Shandong Jinde New Materials Co., Ltd. A method for producing p-acetamidobenzenesulfonyl chloride by a two-stage dual-temperature zone method based on continuous flow reaction: CN201911248993.3[P]. 2021-03-12.

[8]https://www.guidechem.com/msds/121-60-8.html